Mechanism of NASH pathogenesis by nuclear receptors through qualitative changes in fatty acids

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07474
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Gunma University
• Principal Investigator: Inoue Yusuke 群馬大学, 大学院理工学府, 教授 (90304302)
• Co-Investigator(Kenkyū-buntansha): 阪口 政清 岡山大学, 医歯薬学総合研究科, 教授 (70379840) ; 柿崎 暁 群馬大学, 大学院医学系研究科, 講師 (80344935)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脂肪肝 / 核内受容体 / 脂肪酸 / 繊維化

Outline of Final Research Achievements

Non-alcoholic steatohepatitis (NASH) is a malignant disease that progresses to cirrhosis and hepatocelular carcinoma, for which there is no cure. Mice with liver-specific deficiency of the nuclear receptor HNF4α (KO mice) develop NASH, but NASH was ameliorated in double-deficient mice by crossing KO mice with PPARα-deficient mice. Therefore, KO mice develop NASH due to PPARα activation. The activation was found to be accompanied by changes in the composition of fatty acids in the liver. In particular, an increase in oleic acid was proven to activate PPARα.

Free Research Field

病態生化学

Academic Significance and Societal Importance of the Research Achievements

本研究により、脂肪酸組成の変化による核内受容体PPARαの活性化による非アルコール性脂肪性肝炎（NASH）の新しい発症機構が解明できた。本研究で得られた知見は、２つの核内受容体であるHNF4αとPPARαのシグナルカスケードに着目したNAFLD/NASHの新しい診断・治療法の開発に貢献できることが期待される。